Natural killer (NK) cells are bone marrow derived lymphocytes essential for host defense against certain infections and tumors. Upon activation they rapidly produce a range of cytokines and can mediate cytotoxic responses against infected, stressed, or tumorigenic cells. The role of NK cells in chronic inflammatory diseases is emerging, and it is becoming increasingly appreciated that NK cells may play an important role in the modulation of T and B cell responses through their capacity to promote differentiation and maturation of dendritic cells (DC) and subsequent polarization of T cell responses (see, e.g., Cooper et al. (2004) Trends Immunol. 25: 47-52; Zhang et al. (2007) Blood Oct 1; 110(7):2484-93). Furthermore, studies have shown that NK cells have the capacity to directly eliminate subsets of activated T cells via cell-mediated cytotoxic responses (Lu et al. (2007) Immunity. 26: 593-604). NK cell activity is regulated by a complex mechanism that involves both activating and inhibitory signals (see, e.g., Moretta et al. (2001) Annu Rev Immunol 19:197-223; Moretta et al. (2003) EMBO J EPub Dec 18; Ravetch et al. (2000) Science 290:84-89; Zambello et al. (2003) Blood 102:1797-805; Moretta et al. (1997) Curr Opin Immunol 9:694-701.
Several different NK-specific receptors have been identified that are involved in NK cell mediated recognition and killing of HLA Class I deficient target cells. One import inhibitory NK cell receptor is CD94/NKG2A, which interacts with the non-classical MHC class I molecule HLA-E (see, e.g., Braud et al. (1998) Nature 391:795-799; Lee et al. (1998) PNAS 95:5199-5204; Vance et al. (2002) PNAS 99:868-873; Brooks et al. (199) J Immunol 162:305-313; Miller et al. (2003) J Immunol 171:1369-75; Brooks et al. (1997) J Exp Med 185:795-800; Van Beneden et al. (2001) 4302-4311; US Patent application no. 20030095965).
CD94/NKG2A is an inhibitory receptor found on subsets of NK, NKT and T cells, which restricts their killing of cells expressing the CD94/NKG2A-ligand HLA-E carrying small peptides typically derived from the leader sequence of other MHC class I molecules (see, e.g., WO99/28748 and Braud et al. (1998) Nature 391:795-799).
Various antibodies against NKG2A have been described in the art. For example Sivori et al. (Eur J Immunol 1996; 26:2487) refers to the murine anti-NKG2A antibody Z270; Carretero et al. (J Exp Med 1999; 190:1801-12) refers to rat anti-murine NKG2A antibody 20D5; US patent application 20030095965 describes murine antibody 3S9, witch binds to NKG2A, NKG2C and NKG2E; patent application WO06070286 discloses monoclonal antibodies against NKG2A; and patent application WO2008/009545 describes the humanized antibody humZ270 and other anti-NKG2A antibodies with substantially identical variable heavy chain and/or variable light chain to those of Z270.